1 Pharmacokinetic parameters for valproic acid (VPA) were determined before and following 2 weeks of carbamazepine (CBZ) administration in five healthy male volunteers. Mean VPA dosage was 16.4 mg kg-1 day-1. CBZ dosage was started at 100 mg twice daily and increased after 1 week to a total daily dose of 300 mg. 2 After CBZ administration, mean VPA plasma clearance increased from 0.90 ± 0.18 s.d. to 1.26 ± 0.241 h-1 (P < 0.05) as did clearance of free VPA (20.8 ± 7.6 to 37.0 ± 13.6 1 h-1). Mean VPA elimination rate constant increased from 0.051 ± 0.011 to 0.067 + 0.011 h-1 (P < 0.05) after CBZ administration.3 Mean area under the serum concentration vs time curve decreased from 675.0 ± 130.5 to 475.7 ± 75.7 mg 1-1 h (P < 0.05) after CBZ administration. Mean serum VPA half-life decreased from 14.0 ± 2.4 to 10.6 ± 1.4 h (P < 0.05). Mean serum VPA trough concentrations decreased from 44.0 ± 16.7 to 27.0 ± 10.4 ,ug ml-' (P < 0.05).4 A significant change was not observed in the mean VPA volume of distribution after CBZ coadministration suggesting that enzyme induction rather than a competition for plasma protein binding sites was involved in this interaction. 5 Despite the increased clearance of VPA, the urinary recovery of VPA or conjugate did not increase after CBZ administration.